Amides of o, o-dialkyldithiophos-phorylacetic acids



United States Patent 3,238,202 AMIDES 0F 0,0-DlALKYLDlTIHOPHOS- PHORYLACETIC ACID Cesare Augusto Peri and Giorgio Rossi, Milan, ltaly,

assignors to Montecatini Societa Generale per llndustria Mineraria e Chimica, Milan, Italy, a corporation of Italy No Drawing. Filed Apr. 30, 1962, Ser. No. 191,313

Claims priority, application Italy, May 2, 1961, 8,069/61; Apr. 11, 1962, 7,164/62 12 Claims. (Cl. 260-2471) Our invention relates to compounds having the formula l R s wherein R and R are the same or different low molecular weight alkyl radicals with a linear or branched chain, containing a fluorine atom, and R and R are the same or different low molecular weight linear alkyl radicals, a CH SR, CH OR' (wherein R is an alkyl radical) a CN group and hydrogen or form together with the nitrogen atom a morphol-ine nucleus.

Our invention has a further object the miticidal (with a prevailingly ovicidal action) and insecticidal compositions containing one or more compounds comprised in the general Formula 1,

It is known that the alkylamides of 0,0-dialkyldithiophosphorylaceti-c acid have a pesticidal activity. The activity of some compounds belonging to this class is exerted not only against insects but also against mites and their eggs.

We have found that substitution of a fluorine for a hydrogen atom in the alkyl radicals of the ester groups, produces superior results. The activity spectrum against mites and insects becomes in fact more complete.

The distinctive character deriving therefrom consists of the fact that eggs of female mites contacting vegetative surfaces treated with said substances and of female mites sprayed with said substance are inhibited from hatching, when laid on either treated or nontreated vegetative surfaces. Moreover, said substances exert an ovicidal effect also through ingestion by female mites.

These characteristics, in addition to adult-killing activity, make these compounds particularly suitable for the control of mites and insects.

The formulations used for this purpose may contain one or more active substances comprised in Formula 1, associated with substances commonly used in formulation techniques as auxiliary substances, such as solvents, diluents, adhesive, wetting agents and dispersing agents. The active substances hereof may also be suitably associated with active substances of a different nature to give formulations having a different activity spectrum.

By way of illustration, toxicity values towards Warmblooded animals of a compound of our invention are:

LDSO, acute toxicity per os on a white mouse, expressed as rug/kg. of N-methylamide of di-(betafluoroethyl)dithiophosphorylacetic acid=78 (while that of paranitrophenyldiethyl-thiophosphate is 8.2).

LDSO, acute toxicity by intravenous application on white mouse, expressed as mg./kg, of the above-mentioned compound=85 .5 (while that of paranitrophenyldiethylthiophosphate is 5.7).

The compounds of our invention are prepared by reacting the alkaline salts of 0,0-di(fluoro-alkyl)dithio- 3,238,202 Patented Mar. 1, 1966 phosphoric acids with chloroacetamide or N-alkyl-chloroacetamides according to the following equation:

wherein R, R R and R have the aforementioned meaning and Me is an alkaline metal.

' The following examples illustrate the preparation process and the mi-t-icidal, ovicidal and insecticidal activity of the compounds comprised in Formula 1, but it is understood that these examples do not limit the scope of the present invention.

Example 1 14 g. of chloroacetamide are added to a solution of 39 g. of the potassium salt of 0,0-di-(betafluoroethyDdithiophosphoric acid in cc. of acetone. The reaction mixture is refluxed for 1 hour and is then cooled. KCl is filtered off under suction. The solvent is evaporated under reduced pressure and the residue is dissolved in 50 cc. of methylene chloride; after washing with water (30 cc.), drying on anhydrous Na SQ; and evaporation under reduced pressure, 27 g. of an oily substance, consisting essentially of the amide of 0,0-di-(betafluor ethyl)dithiophosphorylacet-ic acid, are obtained,

N calculated=5'.01 N found=4.684.57%

Example 2 40.8 g. of N-methyl-chloro-acetamide are added to a solution of 97.5 g. of sodium salt of 0,0-di(beta-fluoroethyl)dithiophosphoric acid in 200 cc. of water and the mixture is agitated at room temperature (2025 C.) for 70 hours. The oily phase is separated by decantation, the aqueous phase is extracted with 50 cc. of methylene chloride; the extract is added to the oily phase and the entire organic phase is washed twice with Water (50 cc. each time), thus obtaining, as a residue (after drying on CaCl an evaporating under reduced pressure), 83 g. of an oily substance consisting essentially of the N- N calculated=4.77% N found=4.734.65% n =1.5229 D =L386 Example 3 'is formed which is separated by decantation; the mother liquors are extracted with methylene chloride and the extract obtained is added to the organic phase. After washing with water (50 cc. twice) and drying on CaCl the solvent is removed under reduced pressure.

40.5 g. of a clear yellow oil, consisting essentially of N-monoisopropylamide of 0,0-di(beta-fiuoroethyl)dithiophosphorylacetic acid are obtained. A suitable purification can be carried out by dissolving the raw product in ethanol and by reactional precipitation with water,

The product thus obtained, has

N calculated=4.35%; N found=4.384.45% P calculated=9.64%; P found=9.129.13%

Example 4 By using 118 cc. of an aqueous solution of sodium [3,,8-difiuoroethyldithiophosphate with a concentration of 1.98 mols/liter and 24.3 g. of dimethylchloroacetarnide, with the modalities practically similar to those described in Example 1, 51 g. of a clear yellow oil, consisting essentially of the N-dimethylamide of 0,0-di-(beta-fluoroethyl)dithiophosphorylacetic acid are obtained.

The raw product has:

N calculated:4.55%; N found=4.414.47% P calculated:10.88%; P 'found=9.389.78%

Example 5 By using 11-8 cc. of an aqueous solution of sodium {3,B-difluoroethyldithiophosphate with a concentration of 1.98 mols/liter, and 24.3 g. of ethylchloroacetamide, with the modalities practically similar to those described in Example 1, 43 g. of a clear yellow oil consisting essentially of the N-ethylamide of 0,0-di(beta-fiuoroethyl) dithiophosphorylacetic acid are obtained. The product after purification by dissolution in ethanol and fractional precipitation with water, has

N calculated=4.55%; N found=4.86-4.91% P calculated=10.08%; P found=9.509.43%

Example 6 By using 118 cc. of an aqueous solution of sodium 6,,8-difluoroethyldithiophosphate with a concentration of 1.98 mols/liter, and 32.2 g. of a-cyan-isopropyl chloroacetamide, with the modalities practically similar to those described in Example 1, 58 g. of a clear yellow oil, substantially consisting of N (a-cyano-isopropyl) amide of 0,0-di-(beta-fiuoro-ethyl)dithiophosphorylacetic acid are obtained. The product after purification by dissolution in ethanol and fractional precipitation with water has:

N calculated=8.08%; N found:8.128.13% P calculated=8.94%; P found=8.42-8.49%

Example 7 115 cc. of an aqueous solution of sodium-beta-difluoroethyldithiophosphate with a concentration of 2 mols/l. are added to a solution of 30.6 g. methylmercaptomethylene chloroacetamide (obtained by condensation between N-rnethyldichloroacetamide and methylmercaptane in a medium acidified with hydrochloric acid (see Gazzetta Chimica Italiana, 89, 1330 (1959)) in 50 cc. acetone and the whole is agitated.

After 48 'hours the two layers thus formed are separated by decantation; the organic layer is made free from the most part of the acetone by evaporation under reduced pressure, while the residue is poured in water (80 cc.), retaken with methylenechloride (50 cc.) and further washed with water (80 cc.).

The chloromethylene extract is dried on CaCl and then evaporated under reduced pressure until a constant weight is reached.

Thus, 49 g. oily substance, which after some time solidifies completely.

A sample crystallized from ethyl ether has melting point 43.5 -45 C.; the analysis gives the following results:

P calculated=9.l2% P found=9.109.12%

Said substance consists of the methylmercapto methylarnide of the 0,0-di-(betafiuoroethyl)dithiophosphorylacetic acid having the formula:

115 cc. of an aqueous solution of sodium beta,betadifiuoroethyldithiophosphate with a concentration of 2 mols/l. are added to a solution of 33.4 g. ethylmercaptomethyl chloroacetamide (see Gazzetta Chimica Italiana 89, 1330 (1959)) in 50 cc. acetone, and the Whole is agitated.

By working in a way substantially equal to what has been described in the preceding example, 60.5 g. of oily substance are obtained which gives to the analysis:

P calculated: 8.76 P found=8.59%

Said substance consists of the N-ethyl-mercapto methylamide of the 0,0-di-(betafluoroethyl)dithiophosphorylacetic acid, having the formula:

98 cc. of an aqueous solution of sodium beta,betadifluoroethyldithiophosphate with a concentration of 2 mols/l. are added to 23.3 g. methoximethylenchl-oroacetamide, clear uncolored liquid having a boiling point at 0.6 mm. Hg. at=79 C. (prepared by heating the N- methylchloroacetamide with an excess of methanol in a medium acidified with anhydrous hydrochloric acid) and the whole is stirred at 3035 C. for about 3 hours; then the solution is left for 15 hours.

The oily phase thus formed is separated by decantation and the aqueous phase is extracted with methylene chloride (50 cc.); the oily phase and the chloromethylene extract brought together again are washed with water (80 cc.) twice.

After having dried on CaCl and evaporated under reduced pressure, 45 g. of a clear oily substance are obtained as residue and this gives to the analysis:

P calculated=9.58% P found=9.44%

Said substance consists of the methoxymethylamide of the 0,0-di-(betafiuoroethyl)dithiophosphorylacetic acid, having the formula:

Example 10 78 cc. of an aqueous solution of sodium beta,betadifiuoroethyldithiophosphate with a concentration of 2 mols/l. are added to 22 g. n-propoxymethylenchloroacetamide, clear uncolored liquid having a boiling point at 0.4 mm. Hg at 8690 C. (prepared by heating N-methylolchloroacetamide with n-propyl alcohol, in an ethyl acetate solution, in the presence of anhydrous hydrochloric acid) dissolved in 50 cc. acetone and the whole is agitated at '4045 C. for 3 hours.

After having left the mixture for 15 hours, the organic phase is separated, the most part of the acetone is removed under reduced pressure, the residue is retaken with methylene chloride (50 cc.) and the residue is washed twice with water.

After having dried on CaCl and evaporated under reduced pressure, 42.5 g. .ofan oily substance, having a slight yellow colour are obtained as residue and the analysis gives:

P calculated=8.8l%

P found =8.98%

Said substance consists of the n-propoxymethylamide of the 0,0 di (betafluoroethyl)dithiophosphorylacetic acid, having the formula:

FCHnCHrO FCHrCHzO IS Example 11 117 cc. of an aqueous solution of sodium beta,beta difluoro-ethyldithiophosphate with a concentration of 1.98 mols/l. are added to 33 g. chloroacetyl morpholine and the whole is agitated for 6 hours at 35 40 C.

After having left the mixture for hours, an extraction is carried out using 70 cc. methylene chloride; said extract is washed with water (100 cc.) and then with a 2% NaHCO solution (70 cc.) and then with water again (100 00.).

After drying on CaCl and evaporation under reduced pressure, 64 g. residue are obtained, which consists of a clear oily phase the analysis of which gives:

P calculated=8.86% P found=8.458.49%

Said substance consists of the morpholinamide of the 0,0-di-(betafiuoroethyl)dithiophosphorylacetic acid, hav- Example 12 A spray formulation which can be used for the control of mites or mite eggs, is prepared by dissolving parts of N-mehy-lamide of 0,0-di-(beIta-fluoroethyl)dithiophosphorylacetic acid (obtained as in Example 2) in 75 parts of methyl Cellulose (monomethyl ether of diethylene glycol) and then adding 5% of an emulsifier while agitating at room temperature.

In the following examples are reported some data relating to the biological activity of N-methylamide of 0,0-di(beta-fluoroethyl)dithiophosphorylacetic acid obtained by experimental tests carried out for determining the miticidal and ovicidal action according to the following procedure:

The following test mites were used:

Tetraanychus telarius L.

Metatetranychus ulmi Kich., strain sensible (S) to the action .of other miticides.

Metatetranychus .ulmi Koch., resistant strain (R) i.e., relatively less susceptible to the action of other miticides.

With Tetranychus telarius all tests were carried out on French bean plants in pots. With M. ulmi on the contrary they were executed in part on l-year-old apple trees grown in pots and in part on 2-year-old apple trees of the same culture, grown in an open field. The techniques used for these tests were according to the following fundamental scheme:

Tests with plants in pots-From apple or French bean leaves, discs having a diameter of 2.8 cm. are cut. These discs are sprayed with the products to be tested, before or after infestation with adult mites or with mite eggs. Discs of the same size are used for transferring adults thereon (treated or not treated).

Tests with plants in open field.The apple trees are sprayed by means of a pressure pump, some leaves are taken at various intervals and cut in the form of discs which are then infested with adults.

In both kinds of tests, the discs with the mites and the eggs, are kept at 24-26 C. on wet cotton in open Petri boxes for several days after hatching of the controls.

The percentages of the unhatched eggs and the percentage of the dead mites among the newborn mites are are then calculated.

Example 13 Persistence of activity against M. ulmz' eggs (S and R) deposited by untreated female individuals onto apple tree leaves in open field, sprayed with a preparation containing 0.4% of active ingredients.

11 Date of the treatment: July 29, 1960.

b Date of the treatment: Sept. 13, 1960.

In this test with M. ulmi S. the apple trees in open field were subjected to very frequent rains, sometimes for several consecutive days, during the time (20-30 days) elapsed between the treatment and the determination of the ovicidal activity. Nevertheless the product continued to Show its activity on a high percentage of eggs.

0 N 0t determined date.

Example 14 Persistence of activity against M. ulmi S eggs deposited by treated female individuals onto treated leaves.

1 The adultlcidal activity 0! the product did not allow any evaluation of the residual ovicidal effect Example 15 Persistence of activity against T. telarius eggs laid by treated female individuals onto treated leaves. Eggs laid onto the lower page of leaves.

Percentages of unhatched eggs and of dead newborn mites on treated leaves Concentra- Product tion of active After 1 day After 3 After 5 substance, days days percent Eggs Newborn Eggs Eggs mites N-rnonomethylamide of 0,0- 0. 04 58 18 100 di(betafiuoroethyl) dithio- 0. 1 66 72 phosphorylacetic acid. 0. 4 59 100 100 1 The adulticidal activity of the product did not allow any evaluation of the residual ulmi (S and R) eggs and of T. telarius eggs laid (one hour after the treatment) onto untreated leaves.

Percentage of unhatchcd eggs and of dead newborn mites Concentration of Mites active substance, N-rnonornethylamide of 0,0-dipercent (betafluoroethyl)dithiophosphorylacetic acid eggs Newborn mites M.ulmiR 0.04 6 0. 1 29 6 0. 4 73 6 M. ulmiS 0.04 39 0. 1 44 0. 4 91 T. telariusuu 0. 04 45 Example 17 Effectiveness of N-rnonomethylamide of 0,0-di(betafluoroethyl)dithiophosphorylacetic acid directly sprayed onto adult mites on the leaves.

LD 95 (W 1 N-monomethylamide of Mites 0,0-di(betafluorocthyl)dithiophosphorylacetic acid M. ulmi S 1 M. ulmi R- 1 T. telarius. 0. 05

1 DL 95 =rninimurn l concentration of the active substance of the sprayed solution, capable of killing 95% of adults present on the leaves during the treatment.

The insecticidal and, more particularly, miticidal properties of the compounds comprised in general Formula 1 are demonstrated by the following examples:

Example 18 The data reported in the following table were obtained from a test carried out by intrdoucting S-day-old female flies into beakers previously treated with controlled amounts of benzene solutions of the active substances under examination, and leaving the flies in contact with the treated wall for 20 hours.

ACTIVITY ON FLY (M. DOMESTICA) BY TARSAL CONTACT Percent Products Dose mgJmJ mortality after 20 hours h 50 99 Amide of 0,0-(11 (betafluoroethyl) di- 30 94 thiophosphorylacetic acid 20 78 10 27 50 N -rnethylamide of 0,0-di-(betafluoro- 30 94 ethyl) dithiophosphorylacetic acid. 20 60 10 26 Example 19 The data reported in the following table were obtained from a test carried out by treating (by immersion) a population of virgino-parous apterous female aphids, grown in a laboratory on bean plants under standard conditions, with an aqueous dispersion of the suitably formulated substances to be examined.

Activity against aphids (A phis fabae) by immersion:

Products Dose active Percent mortality substance, ppm. after 20 hours Amide of 0,0-di (beta- 400. 00 100 fiuoroethyl) dithiophos- 200.00 98 phorylacetie acid. 100. 00 84 N-rnethylamide of 0,0- 20.00 100 di-(betafiuoroethyl) di- 10. 00 97 thlophosphorylacetic 5. 00 86 acid. 2. 50 41 N-isopropylamide of 0,0- 60.00 100 di (betafluoroethyl) di- 5. 00 75 thiophosphorylacetic acid.

N-dimethylamide of 0,0- 50.00 100 (ll (betafiuoroethyl) di- 5. 00 93 thiophosphorylacetic acid.

N-ethylamide of 0,0-di- 50.00 100 (betafiuoroethyl) dithlo- 5.00 66 phosphorylacetic acid.

a-cyau-isopropylamide of 50.00 100 0,0-di (betafiuoro- 5. 00 59 ethyl) dithiophosphorylacetic acid.

Mercaptornethylamide of 50.00 96 0,0-di (betafluoroethyl) dithiophosphorylacetic acid.

Mereaptoethylamlde of 50.00 93 0,0-di(betafluoroethyl)- dithiophosphorylacetic acid.

Methoxymethylamide of 50.00 97 0,0-di-(betafluoroethyl)- dithiophosphorylacetic acid.

Propoxymethylamide 0f 50. 00 96 0,0-dl-(betafluoroethyD- dithiophosphorylacetic acid.

Morpholinamide of 0,0- 50.00 100 di(betafiuoroetbyl) dithiophosphorylatic acid.

Example 20 The data reported in the following table were obtained in a laboratory test carried out as follows: the hypogeous portion of young bean plants infested with aphids (A phis fabae) is introduced into colored glass pots containing aqueous dispersions of the product to be examined.

The pots are kept under suitable conditions for the insects for 7 days, noting daily the mortality of the aphids living on the epigeous portion of the plants and taking the final reading on the seventh day.

Example 22 The data reported in the following table were obtained by a treatment (in all cases onto 3 peach trees) carried out in open field on July 26, 1960, by carefully spraying 5 all foliage of the plant with a pump working at 30 atmospheres pressure. Before spraying, sprouts highly and uniformly infested with mealy aphid, were marked on each plant of the single repetitions. On the sprouts, 24 and 72 hours respectively after the treatment, the disin- 10 fested leaves were counted.

Activity against peach mealy aphid (Hyalopterus pruni' Geoffrey).

Intensity of the plant disinfestation evaluated at various times after the treatment.

Experimental test Completely disinfested leaves Repetition Infested No. leaves After 241101115 After 72 hours Product Dose migked No. Percent No. Percent N-methylamide of i I 116 115 99 116 100 0,0-di(betafluoro- 0. II 103 103 100 103 100 ethyDdithiophos- III 105 105 100 105 100 phorylacetic acid.

APHICIDAL ACTIVITY AGAINST APHIS FABAE BY SYSTEMATIC ABSORPTION Products Dose active sub- Percent mortality stance, p.p.m. 7th day Amide of 0,0-di(betafluo- 20 100 roethyl)dithiophosphorylacetic acid. Example 23 f 0,04: 1. 100 j1f; 1 Q32 91 The data reported in the following table were obtained g gp p y 40 by a treatment carried out in open field on June 9, 1960 0n peach plants infested with peach Inealy aphid (Hy- N-isopropylamide of 0,0-di 1. 00 100 al r (betafluoroethyDdi-thio- 0.10 00 us pmm Geoffrey) f during nomtal phosphorylacetic acid. spraying treatments several individuals of this species Ndimethylamide of 070m L 00 100 (also due to the constant disposition on the lower page (betafiuoroethyDdi-thio- 90 of leave-s) can escape the spray, this test was effected in phosphorylacetlc acid. order to establish whether and with what intensity the N-ethylarnide of0,0 -di 1.00 100 product under examination is capable of acting on indi- (betafiumethyl)(Wm- 94 viduals which are not wetted directly by the spraying pliosphorylacetic acid.

liquid, namely Whether is has an indirect action. Ac- N-(a-cyan-isopropyl) 1.00 100 f amide of O'Odiwetafiw 0 10 60 cordingly, the product was appl ed by spraying at a pres oroethyl) dithiophossure of 8 atmospheres, operating so that most of the horylacetic ac d. leaves would not be wetted in their lower pages (i.e., Without wetting the numerous aphids laying on the same Example 21 leaves).

The data reported in the following table were obtained from a test carried out as follows: peach and apple twigs, whose leaves are infested, are sprayed with a formulation diluted to 0.001%, 0.01%, 0.1% and 1%, of active substance.

The tested material is then kept at 23-25 C. till the reading of the results (24 hours after the treatment).

IMMEDIATE APHIDIOIDAL ACTIVITY AGAINST VARIOUS APHID SPE- CIES OF AGRICULTURAL INTEREST,

BY DIRECT SPRAYING The following evaluation of the eflfectiveness of the product to be tested was made:

12 11. Morpholinamide of 0,0-di(betafluoloethyndithim phosphorylacetic acid.

Reduction of the infestation Experimental test acid(formulation containing a 0.30"/ of active substance.

We claim:

1. Amide of 0,0-di(betafluoroethyl)dithiophosphorylacetic acid.

2. N methylamide of 0,0-di(bebafluoroethyDdithiophosphorylacetic acid.

3. N-monoisopropylamide of 0,0-di(betafluoroethyl) dithiophosphorylacetic acid.

4. N-dimethylamide of 0,0-di(bet-aflu0roethyl)dithiophosphorylacetic acid.

5. N monoethylamide of 0,0-di(betafluoroethyl)dithiophosphorylacetic acid.

6. N-(a-cyano-isopropyl)amide of 0,0-di(betafluoroethyl)dithiophosphorylacetic acid.

7. Mercaptomethylamide of 0,0 di(betafluoroetl1yl) dithiophosphorylacetic acid.

8. Mercaptoethylannde of 0,0-di(betafiuoroethy1)dithiophosphorylacetic acid.

9. Methoxymethylamide of 0,0-di(betafluoroethyDdithiophosphorylacetic acid.

10. Propoxymethylamide of O,O-di(betafiuoroetl1y1)dithiophosphorylacetic acid.

12. An amide of the formula:

References Cited by the Examiner UNITED STATES PATENTS 2,494,283 1/1950 Cassaday et .al. 260461 2,981,748 4/1961 Metivier 260-461 3,057,774 10/1962 Baker et al. 260247.1 X

IRVING MARCUS, Primary Examiner. 

11. MORPHOLINAMIDE OF O,O-DI(BETAFLUOROETHYL) DITHIOPHOSPHORYLACETIC ACID.
 12. AN AMIDE OF THE FORMULA: 